Regulation of expression of the cell adhesion receptors, integrins, by recombinant human interleukin‐1β in human osteosarcoma cells: Inhibition of cell proliferation and stimulation of alkaline phosphatase activity

Abstract

Recombinant human interleukin-1β, a mediator of osteoblastic cell function, was found to regulate the expression of the cell adhesion receptors, integrins, on human osteosarcoma cells. Interleukin-1β (IL-1β) at picomolar concentrations, specifically elevated approximately six- to tenfold the expression of the β₁ subunit and its associated α subunits, but not the related vitronectin receptor, within 20 hours. Integrin β₁ messenger RNA levels were elevated within 6 hours and peaked to tenfold higher levels after 20 hours exposure to IL-1β in two human osteosarcoma cell lines. The increase in the cell-surface β₁ integrins resulted in a stronger binding of the IL-1β-treated cells to fibronectin. Cell growth was also inhibited by IL-1β cell morphology was altered, and IL-1β-treated cells expressed an approximately two- to threefold higher alkaline phosphatase. This increase in alkaline phosphatase activity was found to be independent of the inhibition of cell proliferation. These data indicate that the β₁ integrin family of cell surface receptors is a target for regulation by IL-1β which also regulates cell proliferation and the expression of the osteoblastic phenotype in human osteosarcoma cells.